<p>This study hypothesized a subtype of Parkinson’s disease (PD) sharing features of nigrostriatal degeneration with dementia with Lewy bodies (DLB) to account for the difficulty of differentiating the two diseases and explored their relationship. Patients with newly diagnosed PD or DLB (<i>n</i> = 128 and 42, respectively) were enrolled along with patients with essential tremor as controls. Based on data from cardiac ¹²³I-metaiodobenzylguanidine scintigraphy and ¹²³I-FP-CIT dopamine transporter single-photon emission computed tomography, the PD group was divided into a non-advanced (PDNA) and advanced (PDA) subgroup. Nigrostriatal degeneration patterns in the PD subgroups and DLB were determined by region-of-interest analysis using FP-CIT uptake and comparative voxel-wise analysis with neuromelanin-sensitive magnetic resonance imaging. PD was then reclassified using FP-CIT binding in the striatum and caudate as an index. PDNA demonstrated highly selective loss in the ventral substantia nigra and putamen. DLB demonstrated conspicuous loss in the dorsal substantia nigra and caudate. PDA shared features with both PDNA and DLB. Using the index, the PD cohort was divided into two major subtypes: PD with and without early decline in caudate FP-CIT uptake (EDCU). PD with EDCU (<i>n</i> = 58) had demographic and imaging findings similar to those of DLB but also a higher caudate-to-putamen binding ratio than DLB. Multivariate analysis found that the age-adjusted caudate-to-putamen ratio correlated significantly with sex and age-at-onset in PD with EDCU but not in DLB. These findings suggested that nigrostriatal degenerative features differed between PD and DLB. Our classification approach may help identify early diagnostic biomarkers differentiating these diseases.</p>